Non-Insulin Dependent Diabetes Mellitus (NIDDM) is estimated to affect 14.5 million people in the US. Complications of diabetes impair the longevity and quality of life, and include heart disease, stroke, retinopathy, neuropathy and nephropathy. In 1992 the estimated total cost of diabetes in the U.S. exceeded $90 Billion. This proposal presents plans for the development of a new animal model of human obesity and NIDDM. The BBZDR/Wor rat will provide the research community with a superb model with which to study the pathogenesis, prevention, complications and therapy of human diabetes. Starting with the BBZDP/Wor rat model of obesity and autoimmunity, we will employ classical genetic techniques to eliminate autoimmune features, and produce animals with a predictable frequency of obesity, impaired glucose tolerance and diabetes. We will evaluate testosterone injections/implantable pellets as a strategy for male fertility enhancement, a key requirement for efficient and commercial breeding efforts. It is our expectation that this new model of NIDDM will increase our knowledge of the most common type of human diabetes and expedite the development of safe and effective pharmaceutical agents for the treatment of this important human disease. Proposed commercial applications: This proposal presents plans for the development of a new animal model of human obesity and NIDDM. The BBZDR/Wor rat will provide the research community with a superb model with which to study the pathogenesis, prevention, complications and therapy of human diabetes.